POSTPRANDIAL METABOLISM OF TRIGLYCERIDE-RICH LIPOPROTEINS IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS BEFORE AND AFTER BEZAFIBRATE TREATMENT

Retarded post-prandial (pp) lipid clearance is potentially a major com ponent of the increased cardiovascular risk incurred by hypertriglycer idaemic noninsulin-dependent diabetic mellitus (NIDDM) patients. The e ffect of bezafibrate (Bz, 400 mg per day for 5 weeks on chylomicron (C M) and remnant clearance after loads of 100 g of fat and vitamin A was therefore explored in 10 male patients (glycaemia 11.9 +/- 3.3 TG 4.5 +/- 2.4 mmol L(-1)). In all subjects CM-TG and retinyl palmitate (RP) were reduced by 50%, but 8-h non-CM (remnant) RP decreased only in in itially mildly hypertriglyceridaemic subjects (-35%, P < 0.05), while in three patients with very elevated initial TG (epsilon(3/3), epsilon (3/2) and epsilon(2/2) genotypes) 8-h remnant RP increased by 100%. Th e decrease in pp CM-TG correlated with that of fasting Sf 20-400 (r = 0.686, P = 0.026), suggesting that improved lipolysis was a major dete rminant of hypolipidaemic effect. Apo CIII synthesis is known to be de pressed by Bz: concentrations were lower under Bz (P < 0.05). A positi ve correlation (r = 0.880, P < 0.001) with fasting TG before treatment and its disappearance after treatment suggested an involvement of hig h concentrations with hypertriglyceridaemia. Post-prandial non-esterif ied fatty acids were decreased by 35 in correlation with a significant (-19%, P < 0.05) improvement in fasting glycaemia (r = 0.801, P < 0.0 05). These results suggest that Bz acts both on lipolysis and on remov al of CM remnants, but that removal can become saturated when lipolysi s is massively improved.